ArticleBMC genomics2018
Large-scale genomic analysis shows association between homoplastic genetic variation in Mycobacterium tuberculosis genes and meningeal or pulmonary tuberculosis.
Article in BMC genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Reporting practices for genomic epidemiology of tuberculosis: a systematic review of the literature using STROME-ID guidelines as a benchmark.The Lancet. Microbe · 2021Pooled it
- Lineage-associated small inversions disruptMicrobiology spectrum · 2026Article
- Host- and pathogen-related determinants of pulmonaryEuropean respiratory review : an official journal of the European Respiratory Society · 2026Review
- South Asian origin and global transmission history ofmSystems · 2025Article
- Deciphering Tuberculous Meningitis: From Clinical Challenges to Novel Models and Pathogenic Pathways.Current topics in medicinal chemistry · 2025Review
- First Indonesian report of WGS-based MTBC L3 discovery.BMC research notes · 2024Article
- PE/PPE mutations in the transmission of Mycobacterium tuberculosis in China revealed by whole genome sequencing.BMC microbiology · 2024Article
- Pangenome Reconstruction ofMicroorganisms · 2023Article
- Distribution and origins ofMicrobial genomics · 2023Article
- Article
- Distribution ofTropical medicine and infectious disease · 2022Article
- Genome-Wide Study of Drug ResistantMicroorganisms · 2022Article
- Deciphering Genetic Susceptibility to Tuberculous Meningitis.Frontiers in neurology · 2022Article
- Genome-wide analysis inMicrobial genomics · 2021Article
- Geno-Spatial Distribution of Mycobacterium Tuberculosis and Drug Resistance Profiles in Myanmar-Thai Border Area.Tropical medicine and infectious disease · 2020Article
- Recent Developments in Tuberculous Meningitis Pathogenesis and Diagnostics.Wellcome open research · 2019Review
- Sequencing and Annotation of the Genome of Mycobacterium tuberculosis MYC004, a Strain Causing Meningitis in Mexico.Genome announcements · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundMeningitis is the most severe manifestation of tuberculosis. It is largely unknown why some people develop pulmonary TB (PTB) and others TB meningitis (TBM); we examined if the genetic background of infecting M. tuberculosis strains may be relevant.
methodsWe whole-genome sequenced M. tuberculosis strains isolated from 322 HIV-negative tuberculosis patients from Indonesia and compared isolates from patients with TBM (n = 106) and PTB (n = 216). Using a phylogeny-adjusted genome-wide association method to count homoplasy events we examined phenotype-related changes at specific loci or genes in parallel branches of the phylogenetic tree. Enrichment scores for the TB phenotype were calculated on single nucleotide polymorphism (SNP), gene, and pathway level. Genetic associations were validated in an independent set of isolates.
resultsStrains belonged to the East-Asian lineage (36.0%), Euro-American lineage (61.5%), and Indo-Oceanic lineage (2.5%). We found no association between lineage and phenotype (Chi-square = 4.556; p = 0.207). Large genomic differences were observed between isolates; the minimum pairwise genetic distance varied from 17 to 689 SNPs. Using the phylogenetic tree, based on 28,544 common variable positions, we selected 54 TBM and 54 PTB isolates in terminal branch sets with distinct phenotypes. Genetic variation in Rv0218, and absence of Rv3343c, and nanK were significantly associated with disease phenotype in these terminal branch sets, and confirmed in the validation set of 214 unpaired isolates.
conclusionsUsing homoplasy counting we identified genetic variation in three separate genes to be associated with the TB phenotype, including one (Rv0218) which encodes a secreted protein that could play a role in host-pathogen interaction by altering pathogen recognition or acting as virulence effector.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.